The drug discovery process is long and arduous. Prospective treatments need to overcome many hurdles along the way to being made available to patients. Hear from The University of Queensland Frazer Institute’s Associate Professor James Wells, an inventor of compound Q-2361, a drug he hopes will be administered to organ transplant patients as a topical cream to prevent and treat skin cancer. 

What stage is your drug discovery project at? 

Dr James Wells: We’re working on making a cream that will deliver our novel drug into the patient’s skin at the correct dose. We are currently working with two contract research organisations, O2H Discovery in India, to produce large amounts of pure drug substance, and Formulytica in Melbourne, Australia, to make a cream that will deliver our drug effectively into the human skin. The next step will be to work with a US company to understand how the drug is being absorbed into the skin and how long it remains active. Currently, the project is progressing extremely well following the award of $344,610 from the National Foundation for Medical Research and Innovation.

Tell us about what it has been like undertaking the drug discovery journey alongside UniQuest’s drug discovery arm, QEDDI? 

JW: Understanding disease processes and identifying the best molecular target to drug is really the work of a scientist. However, working out how to drug that target and bringing that drug to clinical trial is a complex journey that requires specialist knowledge of chemistry, pharmacology, patent law, industry expectations and standards. All of which I have been able to access through QEDDI. Drug development requires a team of experts, and I have thoroughly enjoyed working with, and learning from, the experts at QEDDI.

What hope would this potential drug give to organ transplant patients?

JW: My hope is the drug will develop into a new treatment for transplant patients to make skin cancer a thing of the past. After receiving an organ transplant, patients must take immunosuppressive drugs to help ensure their bodies do not reject the new organs. However, these drugs can increase a patient’s risk of skin cancer, in particular squamous cell carcinomas (SCC) and Kaposi’s Sarcoma. Currently there are no FDA-approved drugs to treat SCCs in these patients, so skin cancers must be managed with regular medical checks and removals over a person’s lifetime until one becomes too advanced and metastasises. Patients are left with few options without risking transplant rejection, and that’s why this new treatment would be life-changing for them.

QEDDI Medicinal Chemistry Team Leader Dr Rebecca Pouwer and Drug Discovery Team Leader Dr Kim Beaumont have been working with Dr Wells on scaling up the manufacturing process and developing the formulation for the potential new drug to fight skin cancer in organ transplant recipients. 

What stage is the project at currently? 

Dr Rebecca Pouwer: We’re now at the stage where we are trying to make sure we can get enough of the drug into the skin to really help these organ transplant recipients who suffer from skin cancer at a much higher rate than the general population. A big part of that is getting the formulation correct, which we are doing in partnership with Formulytica, an Australian Contract Research Organisation (CRO). They will test several formulations for us and see how much of the drug stays in the skin. Ideally, we want a cream formulation with as much of the drug compound in the skin as possible, that also stays there for as long as possible, to effectively fight the disease.  

What are you looking for in terms of a great formulation?

RP: As with any topical formulation there’s always a possibility that our active compound could degrade in the cream or wouldn’t have a long shelf-life in the cream. So Formulytica will also look at the stability of the cream. This process can often take up to a year, so it gives an insight into what a long process it is to come up with something that ends up on the pharmacy shelf. The formulation process is a big part of giving potential partners some confidence in the safety and efficacy of the product. And we will be looking to partner further, or seek additional funding, to take it to the next stage of development which will include studies on safety.

Once you have a formulation you are happy with, what happens next? 

Dr Kim Beaumont: As the Biology lead for this project, I’ll be more involved when we get to the stage of testing for potential toxicity in animals, for example, which is important before you test in human patients. We would test for potential irritation on skin, as well as look at systemic exposure and making sure that the compound is safe in animal studies. James Wells has been a fantastic collaborator, and this is a particularly interesting project due to the unique mode of action because we’re stopping the activity of another drug, rather than targeting the cells themselves. We really like working on this project with [Associate Professor] James [Wells], it’s very novel. 

Is this a typical QEDDI collaboration? 

KB: For every project we have an academic collaborator and some are doing more things in their lab, and some projects we are doing more things in our lab, but always we talk regularly with the academics and they give us advice about the mode of action of their drug target and we help them to make sure any experiments are up to industry standard, because it’s vitally important to have solid data to present to potential partners and also to use eventually to get clinical approval for our compounds. 

What kind of project is an ideal project for QEDDI? 

KB: We’ve taken on a wide variety of projects. The main thing is that the protein target needs to be druggable for small molecules, because we specialise in small molecules, and secondly, that there is a disease indication with a clear unmet medical need. There are many diseases with no good treatment options and we feel strongly that therapeutic research is vital in those areas.  But we’re open-minded. Some projects are novel in that there’s no known drugs which inhibit the target and there’s little known about that target in the potential disease. So, we work with academics to really validate whether their target is both a good and suitable target before we can progress to drug discovery. But other targets are already quite well known, we might have known drugs already that we can work with as tools. Ideally, we would like the opportunity to talk to researchers as early as possible about how to progress a project into drug discovery. 

What is drug discovery at QEDDI, for the uninitiated?

KB: The first stage that we offer is target validation, and making sure it’s a good target in a particular disease that we would want to go after. And then there is developing screening assays, that’s the biology side of things, so we can screen the candidate drugs to make sure they’re hitting our target. Then medicinal chemistry is obviously very important. So, we can either screen a drug library, or we take known compounds, and then modify them to find a new and better or improved drug. As we find lead compounds that look like they are hitting the target, we need to make sure they’re efficacious and we’ll start by looking in vitro, in the lab, to make sure the drug is doing what we want in cells. And then we’ll move into animal models and make sure they’re fighting whatever the disease is in that animal model. Safety is vital, making sure the compounds are well tolerated and not hitting any other unintentional targets in the human body. When we finally have a good candidate, that’s when we move into preclinical development, which is the phase we are now at with Dr Wells’ Q-2361. Following successful preclinical development, we would then plan to start clinical trials in patients.

Contact QEDDI today.